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Identification
- Summary
Polythiazide is a thiazide diuretic used in the management of hypertension and treatment of edema.
- Brand Names
- Minizide, Renese, Renese-R
- Generic Name
- Polythiazide
- DrugBank Accession Number
- DB01324
- Background
A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Polythiazide (DB01324)
- Weight
- Average: 439.882
Monoisotopic: 438.970880311 - Chemical Formula
- C11H13ClF3N3O4S3
- Synonyms
- Polythiazide
Pharmacology
- Indication
Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.
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- Contraindications & Blackbox Warnings
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As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure
- Mechanism of action
As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
Target Actions Organism ASolute carrier family 12 member 3 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
Pathway Category Polythiazide Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Polythiazide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy. Abaloparatide Abaloparatide may increase the hypotensive activities of Polythiazide. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Polythiazide. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Polythiazide. Acebutolol The therapeutic efficacy of Acebutolol can be increased when used in combination with Polythiazide. - Food Interactions
- Avoid alcohol. Alcohol may potentiate orthostatic hypotension.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Renese Tablet 1 mg/1 Oral Pfizer Labs 2005-12-14 Not applicable US 
Renese Tablet 4 mg/1 Oral Pfizer Labs 2005-12-14 Not applicable US Renese Tablet 2 mg/1 Oral Pfizer Labs 2005-12-14 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Minizide Polythiazide (0.5 mg/1) + Prazosin hydrochloride (5 mg/1) Capsule Oral Pfizer Labs 2006-10-05 Not applicable US Minizide Polythiazide (0.5 mg/1) + Prazosin hydrochloride (2 mg/1) Capsule Oral Pfizer Labs 2006-10-05 Not applicable US Minizide Polythiazide (0.5 mg/1) + Prazosin hydrochloride (1 mg/1) Capsule Oral Pfizer Labs 2006-10-05 Not applicable US Renese-R Polythiazide (2 mg/1) + Reserpine (25 mg/1) Tablet Oral UNSPECIFIED 2006-02-06 Not applicable US
Categories
- ATC Codes
- C03AA05 — Polythiazide
- C03AA — Thiazides, plain
- C03A — LOW-CEILING DIURETICS, THIAZIDES
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- G01AE — Sulfonamides
- G01A — ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
- G01 — GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- Drug Categories
- Amides
- Antihypertensive Agents
- Antihypertensive Agents Indicated for Hypertension
- Benzothiadiazines
- Cardiovascular Agents
- Diuretics
- Drugs causing inadvertant photosensitivity
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Heterocyclic Compounds, Fused-Ring
- Hyperglycemia-Associated Agents
- Increased Diuresis
- Membrane Transport Modulators
- Natriuretic Agents
- OAT3/SLC22A8 Substrates
- Photosensitizing Agents
- Sodium Chloride Symporter Inhibitors
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Thiazides
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thiadiazines
- Sub Class
- Benzothiadiazines
- Direct Parent
- 1,2,4-benzothiadiazine-1,1-dioxides
- Alternative Parents
- Secondary alkylarylamines / Organosulfonamides / Benzenoids / Aryl chlorides / Aminosulfonyl compounds / Sulfenyl compounds / Dialkylthioethers / Azacyclic compounds / Organopnictogen compounds / Organofluorides show 4 more
- Substituents
- 1,2,4-benzothiadiazine-1,1-dioxide / Alkyl fluoride / Alkyl halide / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- benzothiadiazine (CHEBI:8327)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 36780APV5N
- CAS number
- 346-18-9
- InChI Key
- CYLWJCABXYDINA-UHFFFAOYSA-N
- InChI
- InChI=1S/C11H13ClF3N3O4S3/c1-18-10(4-23-5-11(13,14)15)17-7-2-6(12)8(24(16,19)20)3-9(7)25(18,21)22/h2-3,10,17H,4-5H2,1H3,(H2,16,19,20)
- IUPAC Name
- 6-chloro-2-methyl-1,1-dioxo-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
- SMILES
- CN1C(CSCC(F)(F)F)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015419
- KEGG Drug
- D00657
- KEGG Compound
- C07766
- PubChem Compound
- 4870
- PubChem Substance
- 46508633
- ChemSpider
- 4704
- 8565
- ChEBI
- 8327
- ChEMBL
- CHEMBL1587
- Therapeutic Targets Database
- DAP000751
- PharmGKB
- PA164748763
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Polythiazide
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Pfizer Inc.
- Dosage Forms
Form Route Strength Capsule Oral Tablet Oral 1 mg/1 Tablet Oral 2 mg/1 Tablet Oral 4 mg/1 Tablet Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 214 °C PhysProp logP 1.90 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.264 mg/mL ALOGPS logP 2.13 ALOGPS logP 1.1 Chemaxon logS -3.2 ALOGPS pKa (Strongest Acidic) 9.31 Chemaxon pKa (Strongest Basic) -3.1 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 109.57 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 90.52 m3·mol-1 Chemaxon Polarizability 37.56 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9884 Blood Brain Barrier - 0.5727 Caco-2 permeable - 0.6601 P-glycoprotein substrate Substrate 0.6985 P-glycoprotein inhibitor I Non-inhibitor 0.7714 P-glycoprotein inhibitor II Non-inhibitor 0.8974 Renal organic cation transporter Non-inhibitor 0.776 CYP450 2C9 substrate Non-substrate 0.6019 CYP450 2D6 substrate Non-substrate 0.8108 CYP450 3A4 substrate Non-substrate 0.5091 CYP450 1A2 substrate Non-inhibitor 0.7786 CYP450 2C9 inhibitor Non-inhibitor 0.5713 CYP450 2D6 inhibitor Non-inhibitor 0.8479 CYP450 2C19 inhibitor Non-inhibitor 0.7738 CYP450 3A4 inhibitor Inhibitor 0.6198 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6625 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.8224 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 3.3534 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8884 hERG inhibition (predictor II) Non-inhibitor 0.8734
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-016v-6598300000-da70dfe63bf7c73c6097 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0000900000-1f40bed1856f91ab8dd6 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0000900000-1b28691ebe78d549eb4b Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00kr-1005900000-f6f0171070ec8783d766 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0079-1100900000-af58e7b7db92191d5bef Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0059-9031000000-1ad13c618ac499e30f6b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-1249300000-2777775b40a5c59c58cb Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 186.8673992 predictedDarkChem Lite v0.1.0 [M-H]- 195.50897 predictedDeepCCS 1.0 (2019) [M+H]+ 187.6533992 predictedDarkChem Lite v0.1.0 [M+H]+ 198.70338 predictedDeepCCS 1.0 (2019) [M+Na]+ 187.2385992 predictedDarkChem Lite v0.1.0 [M+Na]+ 207.44925 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity)
- Specific Function
- Atp binding
- Gene Name
- SLC12A3
- Uniprot ID
- P55017
- Uniprot Name
- Solute carrier family 12 member 3
- Molecular Weight
- 113138.04 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. [Article]
- Frindt G, McNair T, Dahlmann A, Jacobs-Palmer E, Palmer LG: Epithelial Na channels and short-term renal response to salt deprivation. Am J Physiol Renal Physiol. 2002 Oct;283(4):F717-26. [Article]
- Gamba G: The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009 Oct;297(4):F838-48. doi: 10.1152/ajprenal.00159.2009. Epub 2009 May 27. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- Antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Duarte JD, Cooper-DeHoff RM: Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802. doi: 10.1586/erc.10.27. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- Alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- Organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [Article]
Drug created at June 30, 2007 17:21 / Updated at February 21, 2021 18:51